The Lancet. Child & adolescent health · 2026
Safety, antiviral activity, and pharmacokinetics of long-acting cabotegravir plus long-acting rilpivirine in virologically suppressed adolescents living with HIV-1 (IMPAACT 2017/MOCHA): week 96 and end-of-study results from a multinational, phase 1/2, single-arm trial.
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Moore Carolyn Bolton, Baltrusaitis Kristin, Capparelli Edmund V, Lowenthal Elizabeth D, Yin Dwight E, Moye John H, Smith Christiana, Whitton Michael, Harrington Conn M, Crauwels Herta, Van Solingen-Ristea Rodica, Marzinke Mark A, Heckman Barbara, Ace Andi, Ward Shawn, Whitson Kyle, Huang Jenny, Cheung S Y Amy, Best Brookie M, Townley Ellen, Agwu Allison, Ounchanum Pradthana, Mathiba Sisinyana Ruth, Aurpibul Linda, Korutaro Violet, Masheto Gaerolwe, Patel Faeezah, Moodley Evette, Gaur Aditya H, IMPAACT 2017 Collaborators for the IMPAACT 2017 Team
Аннотация
BACKGROUND: Week 24 and week 48 study data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT 2017)/More Options for Children and Adolescents (MOCHA) trial supported the use of long-acting cabotegravir plus long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in adolescents who were virologically suppressed. Having reached the end of the trial, we report the safety, acceptability and tolerability, antiviral activity, and pharmacokinetics of these drugs in adolescents at 96 weeks.
METHODS: In this phase 1/2 non-comparative trial, adolescents (aged 12-17 years, weighing ≥35 kg) with HIV-1 who were virologically suppressed were enrolled across 18 sites in Botswana, South Africa, Thailand, Uganda, and the USA. Participants switched from pre-study antiretroviral therapy (ART) to 4 weeks of daily oral cabotegravir plus oral rilpivirine, followed by 600 mg long-acting cabotegravir plus 900 mg long-acting rilpivirine intramuscular (3 mL each) injections at weeks 4 and 8, and then every 8 weeks through to week 96. There was an optional extension phase of up to 48 weeks to transition to open-label medications or a continued drug access programme, as applicable, based on in-country approval. The 96-week objectives were to evaluate the safety, antiviral and immunological activity of long-acting cabotegravir plus long-acting rilpivirine in adolescents living with HIV, evaluate tolerability and acceptability, and characterise long-term safety and washout pharmacokinetics through to 96 weeks. The trial is registered with ClinicalTrials.gov, NCT03497676, and is complete.
FINDINGS: Between July 26, 2021, and Aug 27, 2022, 144 participants enrolled (median age at study enrolment 15 years [IQR 14-16]; 74 [51%] of 144 female; 106 [74%] of 144 Black or African American). Three participants were lost to follow-up and six prematurely discontinued study treatment (one treatment non-compliance, one eligibility criteria violation, one drug-related adverse event, and three for pregnancy). Median total-exposure duration was 128 weeks (IQR 113-136). Through to week 96, 35 of 144 participants had an adverse event of grade 3 or higher (24% [95% CI 17·6-32·2]); three had a drug-related adverse event of grade 3 or higher (2% [0·4-6·0]). There were no confirmed virological failures through to week 96. Median (5-95th percentile) week 96 observed trough concentrations of cabotegravir (2·96 μg/mL [1·40-5·52]) and rilpivirine (89·5 ng/mL [54·1-152·0]) approximated those in adults. Through to week 96, at least 97% of participants on treatment preferred injectable treatment to daily oral treatment. No grade 3 or higher drug-related adverse events or confirmed virological failures occurred after week 96.
INTERPRETATION: 96-week study data show sustained safety and antiviral activity, favourable pharmacokinetics, and good acceptability and tolerability in adolescents living with HIV who were virologically suppressed, inform the growing global approvals, and support the ongoing clinical use of injectable cabotegravir plus rilpivirine in this age group.
FUNDING: US National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.
METHODS: In this phase 1/2 non-comparative trial, adolescents (aged 12-17 years, weighing ≥35 kg) with HIV-1 who were virologically suppressed were enrolled across 18 sites in Botswana, South Africa, Thailand, Uganda, and the USA. Participants switched from pre-study antiretroviral therapy (ART) to 4 weeks of daily oral cabotegravir plus oral rilpivirine, followed by 600 mg long-acting cabotegravir plus 900 mg long-acting rilpivirine intramuscular (3 mL each) injections at weeks 4 and 8, and then every 8 weeks through to week 96. There was an optional extension phase of up to 48 weeks to transition to open-label medications or a continued drug access programme, as applicable, based on in-country approval. The 96-week objectives were to evaluate the safety, antiviral and immunological activity of long-acting cabotegravir plus long-acting rilpivirine in adolescents living with HIV, evaluate tolerability and acceptability, and characterise long-term safety and washout pharmacokinetics through to 96 weeks. The trial is registered with ClinicalTrials.gov, NCT03497676, and is complete.
FINDINGS: Between July 26, 2021, and Aug 27, 2022, 144 participants enrolled (median age at study enrolment 15 years [IQR 14-16]; 74 [51%] of 144 female; 106 [74%] of 144 Black or African American). Three participants were lost to follow-up and six prematurely discontinued study treatment (one treatment non-compliance, one eligibility criteria violation, one drug-related adverse event, and three for pregnancy). Median total-exposure duration was 128 weeks (IQR 113-136). Through to week 96, 35 of 144 participants had an adverse event of grade 3 or higher (24% [95% CI 17·6-32·2]); three had a drug-related adverse event of grade 3 or higher (2% [0·4-6·0]). There were no confirmed virological failures through to week 96. Median (5-95th percentile) week 96 observed trough concentrations of cabotegravir (2·96 μg/mL [1·40-5·52]) and rilpivirine (89·5 ng/mL [54·1-152·0]) approximated those in adults. Through to week 96, at least 97% of participants on treatment preferred injectable treatment to daily oral treatment. No grade 3 or higher drug-related adverse events or confirmed virological failures occurred after week 96.
INTERPRETATION: 96-week study data show sustained safety and antiviral activity, favourable pharmacokinetics, and good acceptability and tolerability in adolescents living with HIV who were virologically suppressed, inform the growing global approvals, and support the ongoing clinical use of injectable cabotegravir plus rilpivirine in this age group.
FUNDING: US National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.